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Osteogenic differentiation of skeletal muscle progenitor cells is activated by the DNA damage response.
Rosina, M; Langone, F; Giuliani, G; Cerquone Perpetuini, A; Reggio, A; Calderone, A; Fuoco, C; Castagnoli, L; Gargioli, C; Cesareni, G.
Afiliación
  • Rosina M; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • Langone F; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • Giuliani G; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • Cerquone Perpetuini A; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • Reggio A; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • Calderone A; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • Fuoco C; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • Castagnoli L; Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
  • Gargioli C; Department of Biology, University of Rome "Tor Vergata", Rome, Italy. cesare.gargioli@uniroma2.it.
  • Cesareni G; Department of Biology, University of Rome "Tor Vergata", Rome, Italy. cesareni@uniroma2.it.
Sci Rep ; 9(1): 5447, 2019 04 01.
Article en En | MEDLINE | ID: mdl-30931986
Heterotopic ossification (HO) is a pathological condition characterized by the deposition of mineralized tissue in ectopic locations such as the skeletal muscle. The precise cellular origin and molecular mechanisms underlying HO are still debated. In our study we focus on the differentiation of mesoangioblasts (MABs), a population of multipotent skeletal muscle precursors. High-content screening for small molecules that perturb MAB differentiation decisions identified Idoxuridine (IdU), an antiviral and radiotherapy adjuvant, as a molecule that promotes MAB osteogenic differentiation while inhibiting myogenesis. IdU-dependent osteogenesis does not rely on the canonical BMP-2/SMADs osteogenic pathway. At pro-osteogenic conditions IdU induces a mild DNA Damage Response (DDR) that activates ATM and p38 eventually promoting the phosphorylation of the osteogenesis master regulator RUNX2. By interfering with this pathway IdU-induced osteogenesis is severely impaired. Overall, our study suggests that induction of the DDR promotes osteogenesis in muscle resident MABs thereby offering a new mechanism that may be involved in the ectopic deposition of mineralized tissue in the muscle.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Daño del ADN / Diferenciación Celular / Músculo Esquelético / Células Madre Multipotentes Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Daño del ADN / Diferenciación Celular / Músculo Esquelético / Células Madre Multipotentes Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Italia
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